1. Palliative care in motor neuron disease
Gary Hsin, M.D.
November 18th, 2005

2. Using ALS as a model for discussion

3. Amyotrophic Lateral Sclerosis
Progressive, degenerative neurologic disease of unknown etiology
Involves both upper and lower motor neurons
LMN: weakness, atrophy, fasiculation due to denervation of muscles – amyotrophic
UMN: hyperreflexia, spasticity due to lateral corticospinal tract degeneration – lateral sclerosis

4. ALS continued
Muscle atrophy and spasticity in limb and bulbar muscles result in weakness and loss of ambulation, oropharyngeal dysfunction, weight loss, and ultimately respiratory failure.
The mainstay of treatment for ALS patients is still palliative and symptomatic management.
It is important to provide anticipatory guidance, and continue the discussion of goals of care.

5. Pathology & Etiology Motor neuron degeneration and death
Superoxide dismutase type 1 mediated toxicity
Excitotoxicity via glutamate mediated signaling
Cytoskeletal derangements, mitochondrial dysfunction, viral infections, apoptosis

6. Epidemiology & Prognosis
5000 new case in the U.S. per year
90% cases sporadic, 10% familial
Incidence 1.47~2.7 per 100,000 per year
Prevalence 2.7~7.4 per 100,000 per year
70% die within 3~5 years of diagnosis
10~20% survive for more than 10 years
Improved survival associated with younger age of onset, male gender and limb rather than bulbar symptoms

7. Riluzole
Riluzole reduces the presynaptic release of glutamate, but the precise mechanism of action in ALS is unclear. It is postulated that it may be neuroprotective by reducing excitotoxicity that is due to excess glutamate, and it may also act as a glutamate receptor antagonist.

8. Riluzole continued
Clinical trials so far do show that Riluzole improved survival, especially in younger populations, but demonstrated no beneficial effect on bulbar function or muscle strength
The pts who are most likely to benefit are those who have symptoms for less than 5 years, vital capacity >60%, and no tracheostomy. 50mg PO BID.
The implication here based on best available data is that pt with end stage or advanced disease do not seem to benefit from Riluzole. Therefore starting the medication late in the course of the illness or even continuation of the medication in a hospice setting is not warranted.

9. Signs & Symptoms Limb spasticity Hyperreflexia Brisk jaw reflex
Babinski's sign
Pseudobulbar palsy with emotional lability
Focal or multifocal limb weakness & atrophy
Cramps & fasciculations
Dysarthria, dysphagia and/or choking
Tongue atrophy with fasciculations
Claw hand
Fatigue
Dyspnea

10. Secretion management
In ALS there is overall decreased saliva production, sialorrhea is more a poor handling of saliva.
The management is similar for pts with cerebral palsy, MR, oropharyngeal carcinoma, Down syndrome.
Decrease saliva production, or divert and remove saliva

11. Secretion management Glycopyrrolate (Robinul) 1~2mg BID or TID
Benztropine (Cogentin) 0.5~2.0mg QD or BID or Atropine 0.4mg Q4~6 hours
Amitriptyline (Elavil) 10~150mg QHS
Transdermal scopolamine one or two patches every three days
Trihexyphenidyl (Artane) 1 to 2 mg per day slowly increasing to total of 5 to 15 mg daily in three or four divided doses
May also try Clonidine, Levsin
Much data is derived from studies in other neurologic diseases

12. Secretion management
Botulinum toxin injection into the salivary glands appears to be safe and useful in preliminary studies
External beam radiation [3-30 Gy; 3-10 fractions]
Surgical interventions have been tried w/o demonstrated efficacy

13. Secretion management Thick secretions/mucus Increase fluid intake
Humidified air
Propranolol or Metoprolol

14. Secretion management Non-pharmacologic management
Suction machine (not usually helpful for thick mucus, but helpful with sialorrhea)
Mechanical insufflation-exsufflation (In-Exsufflator cough machine)
Manually assisted coughing techniques

15. Secretion management AAN practice parameters

16. Muscle spasm & weakness
Early PT/OT involvement
Variety of assist devices may provide, mobility, support, comfort and increase functionality, i.e. braces, wheelchair, special air beds, head rests, etc.

17. Muscle spasm & weakness
Cramps
Quinine sulfate 200 mg twice a day
Tizanidine 2 to 4 mg by mouth twice daily up to a total dose of 24 mg daily
Carbamazepine 200 mg twice daily
Phenytoin 100 mg once to three times a day
For mild symptoms:
Magnesium 5 mmol once to three times a day
Vitamin E 400 IE twice a day

18. Muscle spasm & weakness
Spasticity
Baclofen 5 to 10 mg twice daily to three times daily
Tizanidine 2 to 4 mg by mouth twice daily up to a total dose of 24 mg daily
Memantine starting at 5 mg daily, increasing by 5 mg a week to a maximum of 20 mg twice a day
Tetrazepam 50 mg at bedtime, increasing by 25 mg a day to a maximum dose of 150 mg taken two to three times a day

19. Pseudobulbar affect
Also known as: pseudobulbar palsy, emotional incontinence, pathologic crying/laughing
The emotional lability is NOT a mood disorder, but is an uncontrolled outburst and is a very troubling symptom for patients.
It is an abnormal affective display that can be seen in about 50% of ALS patients.

20. Pseudobulbar affect Amitriptyline 10~150mg QHS
Fluvoxamine (Luvox) 100~200mg QD
Alternatively may try Lithium or L-Dopa

21. Constipation
Common symptom due to immobility and side effects from opioid, anti-cholinergics, muscle relaxants

22. Pain
Often results from muscle contracture, joint stiffness, and immobility leading to pressure ulcers at later stage of disease

23. Sleep problems Often associated with other symptoms
Identify and treat underlying causes
Use sedative cautiously

24. Dysarthria Speech therapy often helpful early
Computer technology offer many options to assist with patient communication

25. Dysphagia and nutrition
Decreased caloric and fluid intake may lead to worsening of symptoms, such as weakness, muscle atrophy, fatigue
Initially management includes the modification of food and liquid consistency
Discussion of possible PEG placement

26. Dysphagia and nutrition
For optimal safety and efficacy, PEG placement should be performed before the forced vital capacity falls to below 50% of predicted and not in the preterminal phase.
The indications should be to evaluate for symptoms of hunger, choking, sign of inadequate oral intake, and diminished quality of life, rather than a swallow evaluation.

27. Dysphagia and nutrition
Complications for PEG include:
Transient laryngeal spasm 7.2%
Localized infection 6.6
Gastric hemorrhage 1~4%
Death 1.9%
Does NOT prevent aspiration pneumonia
Studies suggest that with PEG survival is prolonged by 1~4 months

28. Dysphagia and nutrition AAN Practice Parameters

29. Respiratory care
It is important to initiate discussion regarding the patient’s goals and how those goal can be best achieved with respect to respiratory care including non-invasive and invasive mechanical ventilation.
Respect the right of patients to refuse or withdraw treatment.

30. Respiratory care
A decrease of VC to <50% is often associated with respiratory symptoms.
A VC of less than 1L or 25~30% of predicted is associated with significant risk of respiratory failure and sudden death.
There are no current guidelines on how frequently to test VC.

31. Respiratory care Dyspnea Oxygen can be administered for hypoxia
Body position such as elevation is often helpful
Chest physiotherapy in the early phase
Opioid can be used to treat dyspnea and benzodiazepines for associated anxiety
Inhaled opioids have not consistently demonstrated benefit; inhaled lidocaine appears to be more efficacious
Oxygen can be administered for hypoxia

32. Respiratory care
Months to years before terminal respiratory failure, symptoms of chronic nocturnal hypoventilation frequently presents and impair the patient’s quality of life.
The symptoms include: daytime fatigue, concentration difficulty, headache, disturbed sleep, nightmares, nervousness, depression, anxiety, tachypnea, tachycardia, diaphoresis, dyspnea, phonation difficulties, reduced appetite, weight loss, gastritis, cyanosis, edema, recurrent URI, dizziness, syncope, visual disturbance, diffuse pain

33. Respiratory care
Non-invasive intermittent ventilation administered at night for 4 hours is an efficient way of alleviating nocturnal symptoms.
It should be made clear that this effort is for the purpose of symptom management and improving the quality of life rather than prolongation.

34. Respiratory care
It is important to explore other means of ventilatory support should it be desired. The goals of such support and when to discontinue such therapies when the goals are no longer being met. Patients need to be reassured that all necessary care will be provided to ensure their comfort.
Non-invasive: Negative pressure body ventilators and oscillators, Intermittent abdominal pressure ventilator, Intermittent positive pressure ventilators (mouth/nasal)
Tracheostomy & ventilation

35. Respiratory care Patients show higher satisfaction with NIV than IV.
Studies show that ventilator dependent patients are not more depressed than patients who are not vent dependent, and can lead meaningful lives.
But there is greater financial, social and emotional burden.
Note self-selection bias

36. Respiratory care AAN Practice Parameter
Why do we disagree with this particular algorithm!

37. Other symptoms Urinary frequency/urgency Peripheral edema Laryngospasm
In the absence of UTI, often due to spasticity that responds well to Oxybutinin
Peripheral edema
Often dependent: elevation, massage, compression hose (r/o DVT)
Laryngospasm
Sudden reflex closure of vocal cords due to variety of stimuli, usually resolves spontaneously
H1 and H2 blocking agents may be helpful

38. Psychosocial and spiritual care
The role of continued support for patient and family cannot be underestimated or overstated.
Bereavement and grief counseling from diagnosis

39. Additional resources ALS Association (www.alsa.org)
Muscular Dystrophy Association (
Links to resources for patients and families
Books:
Learning to Fall: The Blessings of an Imperfect Life, Philip Simmons
Tuesdays with Morrie, Mitch Albom
There are many these are some of my personal favorites

40. Special considerations in pediatrics using SMA (spinal muscular atrophy) as a model